Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The importance of diabetic angiopathy for prognosis and course of diabetes mellitus, possibilities and basis of angiological therapy Complications originating from the vascular system determine life expectancy of the diabetic patient. He is particularly endangered by apoplexy, heart attack, arteriosclerosis of the lower extremities, retino- and nephropathy. Microangiopathy is a specific diabetic problem, the development of which shows a clear dependency on the quality of metabolism. Conventional therapy of circulatory problems today is less concerned with the vascular system than with the qualities of blood viscosity. In this context, viscosity is of main concern. Particularly in microcirculation viscosity is dependent on blood factors such as: haematocrit, plasmaviscosity, erythrocytes and thrombocytes. Their changed behaviour results, in the case of diabetes mellitus, in an increase in viscosity partly dependent on metabolism. A promising concept of treatment is available by pharmaceutically influencing the alteration of erythrocytes.
 ...
PMID:[Diabetes mellitus and microcirculation. Significance of diabetic angiopathy for the prognosis and course of diabetes mellitus, possibilities and bases of angiologic therapy]. 96 91

Microangiopathy related cerebral damage (MARCD) includes early confluent and confluent white matter hyperintensities (WMH) and lacunar lesions. It is expected to be the result of interactions between multiple genetic and environmental factors. The estimated proportion of genetic factors contributing to the interindividual variation seen in WMH volume is 73%. This estimate points to a significant genetic component in WMH development. In the setting of the Austrian Stroke Prevention Study we search for genes being associated with the presence, severity and progression of MARCD using the candidate gene approach. Defining susceptibility genes may allow to better identify individuals at high risk for MARCD and to target preventive measures.
 ...
PMID:Genetic aspects of microangiopathy-related cerebral damage. 1096 13

Microangiopathy-related cerebral damage (MARCD) is a common finding in the elderly. It may lead to cognitive impairment and gait disturbances. Arterial hypertension and age are the best accepted risk factors for MARCD. Genes involved in blood pressure regulation, like genes encoding the proteins of the renin-angiotensin system (RAS) therefore represents good candidate genes for MARCD. Plasma angiotensinogen level is a major determinant of the RAS activity. Positive correlation between angiotensinogen gene expression and RAS activity, as well as blood pressure were observed. Common mutations described in the AGT promoter were able to alter AGT expression in cell culture. We described that 4 frequent mutations at the AGT promoter are combined in 5 haplotypes coded as A (-6:g, -20:a, -152:g, -217:g), B (-6:a, -20:c, -152:g, -217:g), C (-6:a, -20:c, -152:a, -217:g), D (-6:a, -20:a, -152:g, -217:g), and E (-6:a, -20:a, -152:g, -217:a). The B haplotype was significantly associated with MARCD in the cohort of the Austrian Stroke Prevention Study (p = 0.005). The association was independent of hypertension, which pinpointed to a possible role of the local RAS in this relationship. Investigation of the promoter activity of the AGT gene in astrocytes suggests that expression of this gene may be modulated by the haplotype.
 ...
PMID:Microangiopathy-related cerebral damage and angiotensinogen gene: from epidemiology to biology. 1245 50

Nuclear medicine imaging can play an important role in the diagnosis of stroke risk, the differential diagnosis of vascular and parenchymal cerebral abnormalities, and the understanding and management of poststroke recovery. Radionuclide brain-imaging methods can assess hemodynamic, vascular, and metabolic status before and after stroke. Several techniques, including vasodilatory stress imaging with regional cerebral blood flow (rCBF) single-photon emission computed tomography (SPECT), oxygen extraction methods with positron emission tomography (PET), and spectroscopic imaging with magnetic resonance spectroscopic imaging, offer ways to distinguish vascular from parenchymal dysfunction and to determine whether any observed abnormalities in cerebral blood flow are primary or secondary disease manifestations. The value of radionuclide imaging in assessing the efficacy of several interventional surgical procedures is presented. Data from several imaging modalities bearing on the controversial issue of luxury perfusion and reperfusion injury are analyzed, including some of the discrepancies between animal and human clinical data. Imaging evidence for white matter disease and microangiopathy is analyzed, including a quantitative rCBF pattern analysis that distinguishes between typical Alzheimer's disease and microangiopathy by using multivariate analysis of variance curve profile analysis, which shows results of significant differences in the circumferential cortical blood flow profiles at P =.01. Microangiopathy showed rCBF reduction in the frontal and frontotemporal regions as compared with the more typical reduction in posterior temporal-parietal rCBF diminution characteristic of Alzheimer's disease. Several functional neuroimaging approaches to the study of cerebral poststroke reorganization are analyzed in the context of 2 major models of recovery: the resolution of diaschisis and reorganization in spared brain. Research on these issues is presented with SPECT, PET, magnetic resonance imaging, and magnetic resonance spectroscopy. Data show how standard structural magnetic resonance imaging, (99m)Tc hexamethylpropylene amine oxime SPECT, PET imaging, and magnetic resonance spectroscopy can be used to identify the extent of permanent damage versus penumbral and remote effects of a stroke. The results of the analysis of the pure-diaschisis model show a high correlation between the rCBF brain SPECT defect volume in the cortex and the magnetic resonance spectroscopic imaging (MRSI) change in the white matter. There is a statistically significant positive correlation between the 2 (P <.01; r(2) = 0.94). The increased creatine/N-acetyl aspartate and reduced rCBF are proposed to be due to an increase in the white matter creatine component due to diaschisis and the repair mechanisms associated with increased astrocytosis, in addition to a reduction of N-acetyl aspartate in diaschitic white matter. Xenon-133 dynamic SPECT is shown to be a quantitative and sensitive measure of cerebrovascular status and hemodynamic constraints in both spared and affected brain, providing evidence for reorganization and cerebral plasticity. Fluorine-18 PET and (31)P spectroscopic imaging data show reorganizational changes in the contralesional hemisphere after stroke. The phosphocreatine-adenosine triphosphate ratio in the contralesional hemisphere was 38% +/- 17% higher than in the ipsilateral hemisphere. The phosphocreatine-adenosine triphosphate ratio was highly correlated (r = 0.88, P <.05) with increasing (18)F-fluorodeoxyglucose uptake. These results showed that there is a parallel change in glucose metabolism and high-energy phosphate metabolism associated with poststroke recovery that is proposed to be due to cerebral reorganization in the contralateral premotor cortex. The value of these results on rehabilitation strategy, including possible criteria for the use of facilitatory versus compensatory approaches, is analyzed.
 ...
PMID:Neuroimaging in cerebrovascular disorders: measurement of cerebral physiology after stroke and assessment of stroke recovery. 1260 57

As the second cause of death and cognitive decline in industrialized countries, stroke is a major burden for society. Vascular risks factors such as hypertension and diabetes are involved in most stroke patients, aggravate stroke severity, but are still poorly taken into account in preclinical studies. Microangiopathy and sustained inflammation are exacerbated, likely explaining the severity of stroke in those patients. We sought to demonstrate that intravenous administration of human adipose derived-mesenchymal stem cells (hADMSC) that have immunomodulatory properties, could accelerate sensorimotor recovery, prevent long-term spatial memory impairment and promote neurogenesis, in diabetic or hypertensive mice, subjected to permanent middle cerebral artery occlusion (pMCAo). Diabetic (streptozotocin IP) or hypertensive (L-NAME in drinking water) male C57Bl6 mice subjected to pMCAo, were treated by hADMSC (500,000 cells IV) 2 days after cerebral ischemia induction. Infarct volume, neurogenesis, microglial/macrophage density, T-lymphocytes density, astrocytes density, and vessel density were monitored 7 days after cells injection and at 6 weeks. Neurological sensorimotor deficit and spatial memory were assessed until 6 weeks post-stroke. Whatever the vascular risk factor, hADMSC showed no effect on functional sensorimotor recovery or cognitive decline prevention at short or long-term assessment, nor significantly modified neurogenesis, microglial/macrophage, T-lymphocytes, astrocytes, and vessel density. This work is part of a European program (H2020, RESSTORE). We discuss the discrepancy of our results with those obtained in rats and the optimal cell injection time frame, source and type of cells according to the species stroke model. A comprehensive understanding of the mechanisms preventing recovery should help for successful clinical translation, but first could allow identifying good and bad responders to cell therapy in stroke.
 ...
PMID:Intravenous Administration of Human Adipose Derived-Mesenchymal Stem Cells Is Not Efficient in Diabetic or Hypertensive Mice Subjected to Focal Cerebral Ischemia. 3137 78